Ia molecules act as restriction (or co-recognition) elements and as immune response gene products. Thus, they are critical in antigen-recognition by T cells because 1) they are recognized by T cells together with antigen and 2) they appear to interact with and determine the immunogenicity of antigens. A series of I-Ak mutants in functional antigen-presenting cell (APC) hybridomas have been prepared. These are of three general types: Type A mutants, which appear to affect the Akappa/beta chain; Type B mutants, which appear to affect the Akappa/beta chain; and a set of mutants which lead to lack of expression of both AAlpha and ABeta chains. The capability of these mutant APC lines to present antigen to a large panel of I-Ak restricted T cell hybridomas has been evaluated as a first step in the structure-function analysis of these mutants. At the same time, genomic clones of the Akappa/beta genes from mutant lines are being prepared for nucleotide sequencing so as to determine the structural basis of these mutations.